Subjects with histories of stimulant abuse are studied on the Residential Research Unit to determine the abuse liability of mazindol (an anorectant with some psychomotor stimulant properties) to methylphenidate (a prototypic psychomotor stimulant with a known potential for abuse). This study was performed because mazindol has been used in binding studies aimed at isolating the cocaine receptor. The results of these studies indicated that mazindol has high affinity binding at cocaine-sensitive dopamine receptor sites. Mazindol is a theoretically interesting drug since its apparent mechanism of action (blocks reuptake of norepinephine and dopamine) suggests that it would have abuse potential. However, one previous study and limited clinical experience, suggest that it is seldom abused. Therefore additional characterization of the clinical pharmacology of mazindol could be of importance in analytic efforts as well as drug development. This study is conducted in collaboration with the Neuroscience Branch. Subject testing has been completed. Mazindol and methylphenidate increased heart rate and diastolic blood pressure and decreased hunger. Mazindol decreased vigor and increased measures of fatigue and tired and elevated scores on the PCAG and LSD scales of the ARCI. Methylphenidate did not cause the sedative-like effects seen after mazindol. Subjects reported disliking for each drug. These data indicate that at doses three times the therapeutic level mazindol poses little abuse potential. On the other hand its dysphoric effects call to question the acceptability of mazindol for the treatment of cocaine dependence. The data were presented at the 1990 CPDD meeting and a manuscript has been prepared for submission to Pharmacol Biochem and Behavior.